High-performance photosensitizers are highly desired for achieving selective tumor photoablation in the field of precise cancer therapy. However, photosensitizers frequently suffer from limited tumor suppression or unavoidable tumor regrowth due to the presence of residual tumor cells surviving in phototherapy. A major challenge still remains in exploring an efficient approach to promote dramatic photoconversions of photosensitizers for maximizing the anticancer efficiency. Here, a rational design of boron dipyrromethene (BDP)-based conjugated photosensitizers (CPs) that can induce dually cooperative phototherapy upon light exposure is demonstrated. The conjugated coupling of BDP monomers into dimeric BDP (di-BDP) or trimeric BDP (tri-BDP) induces photoconversions from fluorescence to singlet-to-triplet or nonradiative transitions, together with distinctly redshifted absorption into the near-infrared region. In particular, tri-BDP within nanoparticles shows preferable conversions into both primary thermal effect and minor singlet oxygen upon near-infrared light exposure, dramatically achieving tumor photoablation without any regrowth through their cooperative anticancer efficiency caused by their dominant late apoptosis and moderate early apoptosis. This rational design of CPs can serve as a valuable paradigm for cooperative cancer phototherapy in precision medicine.
Hydrogen sulfide (H2S) as an important biological gasotransmitter plays a pivotal role in many physiological and pathological processes. The sensitive and quantitative detection of H2S level is therefore crucial for precise diagnosis and prognosis evaluation of various diseases but remains a huge challenge due to the lack of accurate and reliable analytical methods in vivo. In this work, we report a smart, H2S-responsive and depleting nanoplatform (ZNNPs) for quantitative and real-time imaging of endogenous H2S for early diagnosis and treatment of H2S-associated diseases. We show that ZNNPs exhibit unexpected NIR conversion (F1070 → F720) and ratiometric photoacoustic (PA680/PA900) signal responsiveness towards H2S, allowing for sensitive and quantitative visualization of H2S in acute hepatotoxicity, cerebral hemorrhage model as well as colorectal tumors in living mice. ZNNPs@FA simultaneously scavenges the mitochondrial H2S in tumors leading to significant ATP reduction and severe mitochondrial damage, together with the activated photodynamic effect, resulting in efficient suppression of colorectal tumor growth in mice. We believe that this platform may provide a powerful tool for studying the vital impacts of H2S in related diseases.
Developing endogenous photo‐activated theranostic platforms to overcome the limitation of low tissue‐penetration from external light sources is highly significant for cancer diagnosis and treatment. We report a H2O2‐initiated chemiluminescence (CL)‐triggered nanoparticle aggregation strategy to activate theranostic functions of gold nanoparticles (AuNPs) for effective tumor imaging and therapy. Two types of AuNPs (tAuNP & mAuNP) were designed and fabricated by conjugating 2,5‐diphenyltetrazole and methacrylic acid onto the surface of AuNPs, respectively. Luminol was adsorbed onto the mAuNPs to afford self‐illuminating mAuNP/Lu NPs that could produce strong CL by reaction with H2O2 in the tumor microenvironment, which triggers significant aggregation of AuNPs resulting in enhanced accumulation and retention of AuNPs for activated photoacoustic imaging and photothermal therapy of tumors. We thus believe that this approach may offer a promising tool for effective tumor treatment.
Tumor microenvironment plays a pivotal role in the growth and metastasis of tumors, and has become a promising target for precise diagnosis and treatment of tumors. Herein, a novel smart NIR theranostic probe Cy-1 that can simultaneously respond to low intracellular pH and reductive glutathione (GSH) is reported. This probe has demonstrated to be able to intermolecularly undergo a biologically compatible CBT-Cys condensation reaction to selectively form large nanoaggregates in the tumor microenvironment resulting in its enhanced accumulation and retention in the tumor, which as a consequence significantly improves the sensitivity of NIR/photoacoustic imaging and photothermal therapeutic efficacy of tumors in living mice. We thus believe that this dual stimuli-mediated self-assembly strategy may offer a promising and universal platform for cancer theranostics.
A novel NIR-II probe QT-RGD consisting of a NIR-II fluorophore and two tumor-targeting cyclic-RGD peptides was reported. In vitro and in vivo studies show that it could be successfully used for multimodal NIR-II/PA/SPECT imaging and photothermal therapy of malignant tumor.
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